03150naa a2200325 a 450000100080000000500110000800800410001902200140006002400360007410000310011024501470014126000090028850008150029752013880111265300130250065300210251365300140253465300140254865300080256270000150257070000150258570000170260070000140261770000240263170000180265570000140267370000150268770000220270277301000272410639702023-03-08       2023    bl uuuu     u00u1 u    #d  a1472-97927 a10.1016/j.tube.2022.1022992DOI1 aCOLOMBATTI OLIVIERI, M. A.  aGenomic comparison of two strains of Mycobacterium avium subsp. paratuberculosis with contrasting pathogenic phenotype.h[electronic resource]  c2023  aArticle history: Received 30 September 2022; Received in revised form 28 November 2022; Accepted 19 December 2022; Available online 21 December 2022. -- Correspondence authors: Berná, L.; Unidad de Biología Molecular, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, CP, Uruguay, email:lberna@pasteur.edu.uy ; Santangelo, M.P.; Instituto de Agrobiotecnología y Biología Molecular (IABIMO), INTA-CONICET, Dr. Nicolás Repetto y De Los Reseros S/Nº B1686IGC, Buenos Aires, Hurlingham, Argentina, email:santangelo.maria@inta.gob.ar -- FUNDING: This work was supported by the National Institute of Agriculture Research (grant number PNSA PDI105); National Agency for Science and Technology Promotion, Argentina (grant number PICT 2016-0287); CONICET-Institut Pasteur Bilateral Cooperation Program. --  aIn a previous study, we evaluated the degree of virulence of Mycobacterium avium subsp. paratuberculosis (Map) strains isolated from cattle in Argentina in a murine model. This assay allowed us to differentiate between high-virulent MapARG1347 and low-virulent MapARG1543 strains. To corroborate whether the differences in virulence could be attributed to genetic differences between the strains, we performed Whole Genome Sequencing and compared the genomes and gene content between them and determined the differences related to the reference strain MapK10. We found 233 SNPs/INDELS in one or both strains relative to Map K10. The two strains share most of the variations, but we found 15 mutations present in only one of the strains. Considering NS-SNP/INDELS that produced a severe effect in the coding sequence, we focus the analysis on four predicted proteins, putatively related to virulence. Survival of MapARG1347 strain in bMDM was higher than MapARG1543 and was more resistant to acidic pH and H2O2 stresses than MapK10. The genomic differences between the two strains found in genes MAP1203 (a putative peptidoglycan hydrolase), MAP0403 (a putative serine protease) MAP1003c (a member of the PE-PPE family) and MAP4152 (a putative mycofactocin binding protein) could contribute to explain the contrasting phenotype previously observed in mice models. © 2022 Elsevier Ltd  aGenomics  aOxidative stress  aPhenotype  aVirulence  aWGS1 aFRESIA, P.1 aGRAÑA, M.1 aCUERDA, M.X.1 aNAGEL, A.1 aALVARADO PINEDO, F.1 aROMANO, M. I.1 aCAIMI, K.1 aBERNÁ, L.1 aSANTANGELO, M. P.  tTuberculosis, 2023, volume 138, article 102299. doi: https://doi.org/10.1016/j.tube.2022.102299